1 The Cell Cycle The Importance of the Cell Cycle -prokaryotes: simply divide in two -cell cycle: complex series of stages that eukaryotic cells go through to divide -unicellular eukaryotes: -to reproduce -asexual reproduction -binary fission - multicellular: -growth -repair -replacement -usually develop from a single fertilized egg cell -human cells have 46 chromosomes - organism’s cells dividing into many cells its surface area can keep up with its growing volume -ex: plants have specialized regions at the tips of their roots and stems -repeated cell divisions there produce the new cells that develop into the mature tissues of growing roots, stems, leaves, and other organs -cell division produces many different types of cells that form the nerves, skin, and other organs -the timing of cell division is important -cells in developing tissues pass through the phases of the cell cycle at various rates -allows cells to make identical copies -cell division needs accurate replication and equal division of the genetic information encoded in the cell’s DNA -each new daughter cell must get an identical set of chromosomes -an error in DNA replication or cell division can lead to birth defects, cancer, and other serious diseases -scientists have gained much of what they know about the cell cycle from studies of yeast cells The Stages of the Cell Cycle -as a cell completes the cycle, it becomes two new daughter cells -when a cell divides, its nuclear membrane breaks down -the individual chromosomes separate and become visible as they are distributed to the daughter cells -after cytokinesis, each daughter cell enters G1 where they either commit to the full cell cycle or stay in G0 -different types of cells spend widely different amounts of time in each phase -cells constantly receive signals from their surroundings which sometimes signal the cell to divide -when a cell in G0 or G1 gets these signals they pass through the restriction point, R -this “point of no return” commits the cell to a full round of the cell cycle -once the cell passes R, it can’t return to G1 or G0 without completing a full cell cycle -cell size affects the cell cycle alot ©SarahStudyGuides 2 2 main stages: -interphase: the period between division -the individual chromosomes are not visible in the nucleus -3 stages: 1. G1: gap 1 or prereplication -the cell grows: -makes more cytoplasm -increases in size -as the cell grows larger, the surface area to volume ratio gets smaller -either prepare for the next change or carry out the cell’s special function 2. S phase: DNA Synthesis -DNA replicates -doubles the number of genes in the nucleus 3. G2: gap 2 or premitosis -organelles within the cell replicate -and other materials needed for cell division are produced, like RNA, proteins, etc. -the M phase: -the cell divides -2 stages: -mitosis: nuclear division -4 major stages: prophase, metaphase, anaphase, telophase -cytokinesis: cytoplasmic division -the G0 phase: nondividing cells -it’s stopping point within G1 -these cells exist, but are stuck here don’t pass through the rest of the cycle and don’t divide -skin cells constantly replace themselves, so they are NOT here -brain and nerve cells don’t replace themselves, so they ARE here -this is why brain and spinal cord damage can’t be repaired -liver cells: stays in cell cycle until liver reaches its size then its cells go into G0 If liver is injured: cells hop back in cycle until the liver once again reaches its size -most cells in adult multicellular organisms are in G0 -these cells are metabolically active and specialized to perform the tasks necessary to sustain the life of the organism ©SarahStudyGuides 3 The Race for DNA -James Watson and Francis Crick -1953 -were not expected to succeed -came up with a structural model of DNA that we use today -used an x-ray crystal picture of DNA that Rosalind Franklin took -discovered the structure of DNA -1st attempt: fail -model: very large, metal -invited lots of scientists who told them what was wrong -2nd attempt -asked Rosalind to work with them -she got angry and refused to work with them -Watson saw a picture of DNA that Rosalind took while they were at her place he knew right away that DNA is a double helix Nucleic Acids -nucleic acids store and transmit genetic information -DNA, or deoxyribose nucleic acid, is the genetic material that is inherited from one generation to the next and is reproduced in each cell of an organism -the instructions in DNA are “copied” to RNA, ribonucleic acid, which directs the synthesis of proteins -a nucleic acid is a polymer of nucleotides -a nucleotide is composed of three parts: 1. 5 carbon sugar (pentose) -either ribose or deoxyribose 2. a nitrogenous base -there are 4: adenine, thymine, cytosine, guanine -bases are either single or double rings of carbon, hydrogen, and nitrogen 3. a phosphate group -has a negative charge -the sequence of nucleotides in DNA ultimately determines the sequence of amino acids in protein DNA Structure -DNA molecules consist of two strands called a double helix -in 1953, James Watson and Francis Crick proposed this structure -the backbone, or sides of the DNA molecules are made of sugars and phosphates -the “rungs” of the DNA molecule are made of 2 nitrogenous bases -base pairing depends on how many hydrogen bonds each nitrogen base can form with its counterpart -cytosine only pairs with guanine and thymine only pairs with adenine ©SarahStudyGuides 4 -cytosine only pairs with guanine because 3 hydrogen bonds hold them together, and adenine only pairs with thymine because two hydrogen bonds hold them together -purines are paired with pyrimidines A– – – – – – – T G – – – – – – –C -the sugar-phosphate backbones are facing opposite directions -because the strands are parallel but run in opposite directions, the structure is called antiparallel -covalent bonds—between sugars and phosphates and between sugars and bases -hydrogen bonds—between base pairs -while DNA is a double strand, RNA is a single strand -DNA forms the chromosomes, units of genetic information, that pass from parent to offspring -DNA structure: sugars (deoxyribose) phosphate group Nitrogenous bases adenine = thymine 30% 30% guanine = cytosine 20% 20% Erwin Chargaff’s rules: -each complement base is equal in amount -all four together make 100% ©SarahStudyGuides 5 DNA Synthesis -occurs during the S phase of the cell cycle -this is a critical step in the cell cycle because it replicates the DNA, so one of each identical chromosomes can go to the new cells -the structure of DNA is important in understanding how DNA replicates -the overall structure of the molecule is a double helix -the backbone of the molecule consists of alternating sugars and phosphates held together by covalent bonds -the rungs of the DNA molecules are composed of nitrogen pairs -a purine (adenine or guanine) is always bonded to a pyrimidine (thymine or cytosine) -if u look at the alternating sugar and phosphate bonds on one side of the DNA ladder and compare them to the opposite side you will see: they are facing in opposite directions—one faces up, the other faces down -this structure is referred to as antiparallel and is important in determining the direction in which the new strands of DNA are synthesized -the process can be divided into 3 major parts: 1. binding of enzymes to existing DNA 2. unwinding of the double helix 3. synthesis of new matching strand for each existing strand -these enzymes and proteins are: -helicase- unwinds double helix -topoisomerase- prevents tangling of helix -single strand binding proteins- prevent strands from rejoining -DNA polymerase -breaks hydrogen bonds between nitrogenous bases -brings in new DNA nucleotides -works 5’ to 3’ -RNA primase: -puts in 3-5 RNA nucleotides to which the DNA nucleotides can attach -DNA polymerase-replaces RNA nucleotides -“proofreads” for errors *DNA polymerase can’t add or join new DNA nucleotides to something that’s not there so RNA primase is used to put in RNA nucleotides that the DNA nucleotides can attach to -think of it like painting a black table yellow: -you can’t just paint the table yellow (yellow paint = DNA nucleotides from DNA polymerase) -you need a white coat called primer (primer = RNA nucleotides from RNA primase) -the primer isn’t the final color, the yellow replaces the primer (RNA nucleotides get replaced by DNA nucleotides) -a replisome consists of all of the enzymes listed above as well as the strand of DNA being copied -replisomes move in both directions ©SarahStudyGuides 6 -when the DNA molecule “unzips”, it separates into two strands when the hydrogen bonds between base pairs are broken -this “unzipping” process occurs in many locations throughout the length of the chromosome -these specific sites are called replication origins -multicellular organisms: have many replication origins and replisomes -bacteria: have one replication origin and replisome -DNA “unzips” at many places and has many replication origins -more efficient replication is faster -the “unzipping” results in exposed bases on each side of the DNA ladder -you might expect that new DNA nucleotides would come in to base pair with the exposed bases -however, the enzyme DNA polymerase can only add new nucleotides to a pre-existing strand of DNA -so instead, the enzyme RNA primase first adds a short strand of RNA nucleotides, called a RNA primer, to being the replication process -the RNA nucleotides will later be replaced with DNA nucleotides -once a few nucleotides of FNA primer are in place, the enzyme DNA polymerase begins adding new DNA nucleotides -remember: a nucleotide consists of sugar (deoxyribose), a phosphate group, and a nitrogenous base (A, T, G, or C) -the nitrogenous base sequence of the existing DNA strand determines the base sequence of the matching strand -ex: wherever thymine is on the original strand, adenine is added to the new strand -the synthesis of the two new sides of the DNA molecule occurs in opposite directions -always from 5’ to 3’ -one new strand is synthesized continuously into the replication fork this is the continuous or leading strand -the other new strand is synthesized in short segments out of the replication fork this is the discontinuous or lagging strand -these short pieces are called Okasaki fragments and are eventually joined together by an enzyme called DNA ligase -the overall process results in two identical copies of the DNA molecule -this process is called semiconservative replication —each DNA molecule consists of half “old” and half “new” DNA -after replication, the DNA strands, called daughter strands, will be more compactly stored in the cell -to do this, the DNA is wrapped around proteins called histones which are further bundled together to form nucleosomes -nucleosomes- a group of usually 8-10 histones -allows DNA to take up a lot less space -this coiling results in the highly coiled chromosome structures that are visible during mitosis in the cell cycle ©SarahStudyGuides 7 DNA replication: -the DNA molecule unzips -DNA polymerase adds DNA nucleotides from 5’ to 3’ -DNA polymerase adds new DNA nucleotides continuously INTO the replication fork on the leading strand -DNA polymerase adds new DNA nucleotides OUT of the replication fork on the lagging strand -the lagging strand is added in pieces called Okazaki fragments -DNA ligase is an enzyme that connects the fragments of the lagging strand -the parental strands are the template or mold -DNA unzips at many replication origins-more efficient: replication is faster -the replication bubbles expand -the red = the new strands being added by DNA polymerase -the blue = the parental strands ECT -Semiconservative replication: A ---T G ---C T ---A C ---G parental strand A G T C T C A G the enzyme helicase unzips the DNA molecule A G T C T C A G A G T C T C A G -DNA polymerase adds new DNA nucleotides -two identical strands of DNA: daughter strands ©SarahStudyGuides 8 DNA Repair -a mutation occurs when there is any change in the sequence of a cell’s DNA -mutations may be nonharmful or silent, harmful, or sometimes lethal -the new DNA strands must be exact complements of the parental strands -the likelihood of mistakes occurring is reduced because the enzyme DNA polymerase proofreads and corrects any errors that occur during replication -the process called excision repair is when the mutations are repaired -when mistakes are detected, the mistakes are “cut out” and replaced with the correct nucleotides -mutagens are chemicals that are environmental factors that cause mutations -while mistakes can still occur, the proofreading activity by DNA polymerase reduces the number of mistakes from 1 in 10 thousand base pairs to only 1 in 10 million base pairs -most mutations are known as mismatches because they consist of base pairs that cannot form hydrogen bonds (like adenine and cytosine- they can’t pair up no matter what) -mutations that persist to the next cell division are inherited by the daughter cells -many scientists believe that the accumulation of many of these mutations over a lifetime may result in different types of cancer ©SarahStudyGuides 9 Mitosis and Cell Division The Stages of Cell Division -it’s important that the process of cell division occur correctly because this process produces 2 new cells and if it doesn’t, then the cells can be produced incorrectly with mistakes and they won’t survive -chromosomes are units of genetic information -they are made of DNA molecules -chromosomes are found in the nucleus -when do you call chromosomes what???: -chromatin: when chromosomes are all tangled together -during interphase and telophase and cytokinesis -sister chromatids: when chromosomes are replicated and attached together by a centromere -during prophase and metaphase -chromosome: when chromosomes are long and individual -during anaphase -there are 46 chromosomes in our cells -chromosomes are composed of chromatin -in the early stages of mitosis, the chromatin is condensed and becomes visible, and untangles and coils back on itself -chromatin: mostly made of DNA and also protein (histones) -the DNA is able to fit into the nucleus of the cell: -the DNA is packaged the DNA molecules are wrapped around histone proteins which are grouped together, in groups of 8-10 histones, called nucleosomes -the centromere joins together the sister chromatids -it’s found at the center of the chromosomes -separation of the chromatids is called chromosome segration -if segregation occurs correctly, each new nucleus receives one copy of each chromosome -a mistake at this stage would be one nucleus with two chromosomes and the other nucleus with none daughter cells with this mistake are celled aneuploid cells -Interphase (G1—S—G2) -chromosomes appear in the form of chromatin— appears as a dark granular mass, so you can’t really see the chromosomes -chromatin: mostly DNA and proteins (histones) -chromosomes have replicated during the S phase -the 3 events: -G1-prereplication -S-DNA synthesis -G2- premitosis ©SarahStudyGuides 10 -the 4 stages of mitosis: -the result of mitosis is the production of two nuclei each with a duplicate set of chromosomes -scientists still don’t completely understand how chromosomes move during mitosis 1. prophase -the longest phase of mitosis -begins when the nuclear membrane breaks down into small vesicles -early prophase: -the chromatids become visible because the chromatin has condensed and thickened -the chromosomes appear as two identical sister chromatids -sister chromatids are attached at the centromere -contents of the nucleolus and nuclear membrane disperse and they appear to disappear -centrioles, which are normally found outside the nucleus, separate and move to opposite sides of the nucleus -the centrioles contain tubulin, a microtubule protein -late prophase: -the spindle, a network of proteins that helps to move the chromosomes apart, is produced from the centrioles -spindle fibers begin to attach to the sister chromatids at their kinetochores -near the end of prophase, the coiling of the chromatids becomes tighter -sister chromatids appear short and thick coiled back on themselves so it’s easier to move around *even though plants don’t have centrioles, they still produce spindle fibers which help to pull the chromosomes apart 2. metaphase -the shortest phase of mitosis -sister chromatids align at the equator or metaphase plate -spindle fibers attach to the kinetochores of each chromatid -the spindle, which are arranged in the starlike pattern around the poles of the spindle, are often called asters which is the greek word for star 3. anaphase -sister chromatids separate as spindle fibers shorten -begins when centromeres that join the sister chromatids spit -this causes the chromatids to split and form separate chromosomes -the chromosomes continue to move until they have separated into two groups -each group is now found near the poles of each of the spindles -ends when the chromosomes have stopped moving 4. telophase - chromosomes uncoil to form a tangle of chromatin -this occurs in two regions—where the nuclei of the daughter cells will form -the nuclear envelope reforms around the chromatin -the spindle breaks apart and the nuclear envelope and nucleolus once again become visible ©SarahStudyGuides 11 -this marks the end of mitosis Cytokinesis -often occurs during telophase - the cytoplasm of the cell divides -this results in the production of two complete and individual daughter cells -cytokinesis is different in plant and animal cells: -plants: -cell plate forms from the center of the cell outward -plants don’t have centrioles -animals: -cleavage furrar: how and where the cytoplasm divides Differences in Mitosis -although the major events of cell division are similar in all eukaryotic cells, there are subtle differences -cytokinesis begins during anaphase in most animal cells -plants don’t have centrioles -the biggest difference between cell division in animal and plant cells is due to the fact that plants have cell walls -at cytokinesis in plants, vesicles containing cellulose begin to gather between the two nuclei -these vesicles then begin to fuse, forming the plasma membrane of the two new daughter cells -the contents of the vesicles complete the cell wall between the two new cells -in some fungi like yeast, the nuclear envelope forms a bud instead of breaking down, and the spindle poles are embedded in the nuclear membrane -Key Terms -cell division: the process by which a cell divides into two daughter cells -mitosis: process by which the nucleus of a cell is divided into two nucei, each with the same number and kinds of chromosomes as the parent cell -cytokinesis: process by which the cytoplasm divides into two daughter cells -chromosome: threadlike structure in a cell that contains the genetic information that is passed on from one generation of cells to the next -chromatin: a tangled mess of chromosomes that is composed of DNA and proteins -chromatids: two identical chromosomes attached at their centromere -centromere: structure that holds together each pair of chromatids -cell cycle: period from the beginning of one mitosis to the beginning of the next -interphase: period of the cell cycle between cell divisions -kinetochore: the protein on the centromere for spindle fibers to attach to -prophase: first phase of mitosis in which the chromatids become visible -centriole: structure involved in mitosis that contains a microtubule protein called tubulin ©SarahStudyGuides 12 -spindle: meshlike structure of centrioles that appears to guide the movement of chromosomes during mitosis -metaphase: second phase of mitosis in which the chromatids line up across the equator -anaphase: third phase of mitosis in which sister chromatids separate -telophase: final phase of mitosis where the chromosomes uncoil to form chromatin, and the nuclear envelope and nucleolus reform in each daughter cell ©SarahStudyGuides